Cardiac muscle (and in particular the cardiac purkinje fibre) is a complicated syncytium with narrow restricted extracellular spaces (RECS). Ion concentrations are not constant in these RECS but fluctuate with heart rate and also within each cardiac cycle. The concentration oscillations are important in both normal and pathological cardiac electrophysiology. The present grant proposal uses the voltage clamp technique and extracellular ion sensitive microelectrodes to investigate the role played by concentration oscillations in generating pacemaker activity and controlling the action potential duration in normal and pathological purkinje fibre activity. Since gated membrane conductances are difficult to study in the presence of ion accumulation and depletion, a new purkinje fibre preparation with wide clefts from the canine heart will be studied. Preliminary investigation suggests that this preparation should minimize the problems of ion accumulation and depletion while still permitting the investigation of the properties of the pacemaker current.